Catálogo de publicaciones - revistas

<jats:title>Staying in Place</jats:title> <jats:p> The primary cilium is found on nearly all mammalian cells and is a key regulatory organelle for proper signal transduction throughout development and in adults. Extracellular signal transduction, such as that promoted by Sonic hedgehog (Shh), requires the enrichment of receptors and downstream signaling components in the ciliary membrane. Intraflagellar transport is involved in selective trafficking of proteins into the cilium, but it is not known how these proteins are retained in the cilium. It has been speculated that a diffusion barrier exists at the base of the ciliary membrane. Now, <jats:bold> Hu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="436" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1191054">436</jats:related-article> , published online 17 June) demonstrate directly that a membrane diffusion barrier is indeed present at the base of the ciliary membrane. SEPT2, a member of the septin family that also forms a diffusion barrier in budding yeast and mammalian sperm membranes, localizes to the base of the ciliary membrane and is required for ciliogenesis, ciliary membrane protein localization, and cilium-dependent Shh signaling. </jats:p>

<jats:title>Making the Final Cut</jats:title> <jats:p> RNA splicing, which involves selectively cutting and pasting messenger RNA to generate different proteins, is critical in regulating human physiology and diseases. However, our knowledge of the underlying rules governing splicing regulation remains incomplete. The recent emergence of next-generation sequencing and other high-throughput technologies has provided an opportunity to transform our understanding of RNA regulation. <jats:bold> Zhang <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="439" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1191150">439</jats:related-article> , published online 17 June) combined multiple data sets to generate a robust and relatively complete picture of splicing regulation by the mammalian neuronal splicing factor Nova in the brain. About 700 splicing events were identified, including many novel target exons, some likely to be involved in neurological disease. Combining genomic studies with computational biology also yielded insight into the regulation of alternative splicing. </jats:p>

<jats:title>Location, Location, Location</jats:title> <jats:p> The genome receives epigenetic marks throughout development that regulate the activity of multiple genes. One such mark is methylation, which usually represses gene transcription. Methylation has generally been studied in the promoters of genes, where many regulatory signals coordinate to control the expression of the gene. Studying neural stem cells from mice, <jats:bold> Wu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="444" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1190485">444</jats:related-article> ) now show that DNA methylation can be a double-edged sword. Although methylation of DNA sequences in promoters tends to be repressive, methylation of DNA sequences beyond the promoters can actually promote gene expression. Analysis of the methyltransferase Dnmt3a in mouse neural stem cells revealed that methylations around neurogenic genes—but outside their promoters—maintained the activity of these genes. </jats:p>

<jats:title>Complex I Under Scrutiny</jats:title> <jats:p> Mitochondrial complex I is a large macromolecular membrane complex that couples electron transfer to proton pumping across the mitochondrial membrane and helps to drive adenosine 5′-triphosphate synthesis. <jats:bold> Hunte <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="448" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1191046">448</jats:related-article> , published online 1 July) now describe the structure of complex 1 from the aerobic yeast, <jats:italic>Yarrowia lipolytica</jats:italic> . The sites involved in redox chemistry are distant from those that pump protons, and the structure suggests that a 60-angstrom-long helix is involved in transducing energy to the proton-pumping elements. </jats:p>

<jats:title>Heme Communication Revealed by Asymmetry</jats:title> <jats:p> An electronic bus bar is an electrical conductor that connects several circuits. <jats:bold> Åšwierczek <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="451" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1190899">451</jats:related-article> ) now find that a similar strategy is used by the protein cytochrome bc <jats:sub>1</jats:sub> that plays a central role in cellular respiration and photosynthesis. Protein engineering was used to break the symmetry of a cytochrome bc <jats:sub>1</jats:sub> homodimer, which revealed that the dimer is bridged by electron transfer between two hemes. This allows electrons to move freely within and between dimers to distribute between four catalytic sites. </jats:p>

<jats:title>Fat's Mixed Messages</jats:title> <jats:p> Certain metabolic disorders, such as type 2 diabetes, are more prone to arise in obese individuals, a link that has been attributed, in part, to the detrimental activities of adipokines—proteins secreted by fat cells. Most adipokines disrupt glucose homeostasis by promoting inflammation and insulin resistance. <jats:bold> Ouchi <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="454" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1188280">454</jats:related-article> , published online 17 June; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5990" page="397" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193404">Oh and Olefsky</jats:related-article> </jats:bold> ) identify a new adipokine, secreted frizzled-related protein 5 (Sfrp5), which has the opposite effect: It is anti-inflammatory and appears to promote metabolic health. In obese mice, Sfrp5 suppresses the activation of key inflammatory cells (macrophages) residing within adipose tissue by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. Further study of this Sfrp5-JNK1 regulatory axis in fat may offer therapeutic opportunities for obesity-linked metabolic disorders. </jats:p>

<jats:title>Brain Over Muscle</jats:title> <jats:p> Mutations in the gene encoding the Kir6.2 subunit of the adenosine triphosphate (ATP)–sensitive potassium (K <jats:sub>ATP</jats:sub> ) channel cause a specific type of neonatal diabetes in humans, known as iDEND, which is often accompanied by muscle weakness of unknown etiology. By studying mice expressing the mutant gene only in muscle or only in nerve, <jats:bold> Clark <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="458" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1186146">458</jats:related-article> , published online 1 July) found that the motor impairments originate from inappropriate activation of the channel in the central nervous system rather than in muscle. Patients with iDEND are often treated with sulphonylurea therapies that block K <jats:sub>ATP</jats:sub> channels in both brain and muscle, and these drugs can have adverse effects on heart muscle. Drugs with greater specificity for K <jats:sub>ATP</jats:sub> channels in the brain may thus be a safer option. </jats:p>

<jats:p>The human genome has been called the "blueprint of life," but it's really more of a parts list. Cellular architecture is better defined by its complexes, the molecular machines that actually make a cell, a cell. French researchers first coined the term "interactome" in 1999; the first protein-protein interactome data appeared in 2000. Today the field--like the 11-year-old it is--is maturing rapidly. Interactome research has racked up more than 560 publications, and databases now house interactions numbering in the hundreds of thousands. Still, as international efforts to map the human protein-interaction network get under way, it's clear interactomics has a long way to go.</jats:p>

<jats:p>The show includes a microbicidal gel for preventing HIV infection, dams plans for Patagonia, turbulent moss spore dispersal, and more..</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>